Contrast venography, the gold standard for the diagnosis of deep-vein thrombosis: improvement in observer agreement.

To determine whether the Rabinov-Paulin or the long-leg venography technique should be preferred in the diagnostic management of patients with clinically suspected deep-vein thrombosis, two independent experienced radiologists blindly assessed two different series of venograms of consecutive outpatients with clinically suspected deep-vein thrombosis. Venograms were obtained from two outpatient clinics of primary referral centres. In one centre the venograms were performed according to the technique of Rabinov and Paulin with the use of 100 ml of radiographic material and spot films of the calf, popliteal and more proximal veins. In the other centre, long-leg films were obtained after the administration of 150 ml of contrast material. The percentage venograms adjudicated as inadequate by at least one radiologist and inter-observer disagreement for both series were used as the main study outcome measures. Prior to the study, both radiologists agreed on the standardized criteria for a normal, abnormal and inadequate test result using a separate set of films. An inadequacy rate of 20% was found for the Rabinov-Paulin venography series (n = 123), whereas only 2% of the 126 long-leg films were inadequate for interpretation (p less than 0.001). The inter-observer diagreement for inadequacy, presence or absence of deep-vein thrombosis was 21% for the Rabinov and Paulin venograms and 4% for the long-leg films (kappa, 0.65 and 0.92; 95% confidence intervals: 0.53 to 0.77 and 0.84 to 0.99, respectively; p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Disturbed liver function in heart transplantation candidates: two case reports

Heart transplantation candidates frequently have a disturbed liver function. Two cases with jaundice are described in whom the cause and prognosis of the associated liver disease were analysed. In the 4-yr period during which heart transplantation patients with a disturbed liver function were investigated, "cirrose cardiaque" was not encountered; liver tests usually normalized after a successful heart transplant.     

Chloroquine interaction with inflammatory human polymorphonuclear leucocytes

The molecularin vitro association of radiolabelled chloroquine (CQ) with both normal resting and inflammatory polymorphonuclear leucocytes (PMNs) was measured. For this purpose a suitable ligandassocation assay was developed to measure the cell association and the intracellular concentration of CQ. Under the influence of inflammatory stimuli PMNs display altered interaction with CQ. The intracellular concentration of CQ is reduced with 30 to 40% under inflammatory (disease) states when compared with non-inflammatory conditions. The mechanisms of CQ-PMN interaction associated with these altered intracellular concentrations of CQ are considered, with particular attention to the effects of rheumatic disease. Association experiments of CQ with PMNs performed in the presence of different established transport inhibitors showed that both diffusive uptake and carrier-mediated transport are involved in the cell accumulation of CQ in inflammatory PMNs. From these results, emphasis is given to three explanations for the decrease of the intracellular CQ concentration in inflamed PMNs:

1. the expansion of the PMN volume under inflammatory conditions;
2. the cytoplasmic or lysosomal pH changes and activation of the PMN Na⁺/H⁺ antiport by inflammatory stimuli; and
3. the exocytic release of the granules (degranulation).

Our data suggest that all these mechanisms, based on the events involved in inflammatory responses, may be involved in the decrease of the intracellular CQ concentration in inflammatory PMNs.     

Assessment of bioequivalence after subcutaneous and intramuscular administration of urinary gonadotrophins

The objective was to demonstrate bioequivalence between s.c. and i.m. administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio 3:1). In two randomized, single-centre, cross-over studies, 18 healthy volunteers on each formulation were assigned to one of the two administration sequences. Subjects were given single doses of one of the above gonadotrophins after endogenous gonadotrophin production had first been suppressed using high-dose oral contraceptive. Subsequently, rate (Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax and AUC, analysis of variance (ANOVA) was performed on log-transformed data and for tmax ANOVA was performed on ranks. Intramuscular and s.c. injections of Humegon were bioequivalent with respect to the main pharmacokinetic parameters, being AUC and Cmax of FSH absorption. Intramuscular and s.c. injections of Normegon were bioequivalent with respect to the AUC of FSH and not bioequivalent with respect to the Cmax of FSH. For tmax of FSH as well as for most LH variables of both preparations, bioequivalence could not be proven due to the high intra- and interindividual variability and/or concentrations being close to the detection limit. Thus, the main pharmacokinetic FSH variables after i.m. and s.c. administration of Humegon and Normegon were bioequivalent.      

Immunogenicity of 20 μg of recombinant DNA hepatitis B vaccine in healthy neonates: A comparison of three different vaccination schemes

The immunogenicity of a full dose (20 μg) of recombinant DNA yeast-derived hepatitis B vaccine (Engerix-B) was assessed in healthy neonates in order to compare three candidate vaccination schemes. After randomization 162 newborns of hepatitis B surface antigen (HBsAg) negative mothers entered the study. Neonates received hepatitis B vaccine according to a fourdose vaccination scheme starting either at month 3 (scheme I: months 3,4,5, and 11) or at birth (scheme III: months 0,1,2, and 11). Another group of neonates received hepatitis B vaccine according to a three-dose scheme starting at birth (scheme II: months 0, 1, and 6). Serious adverse reactions were not observed; 2.5% of the vaccinated newborns suffered mild transient local symptoms. The vaccine was highly immunogenic irrespective of vaccination scheme; all infants developed anti-HBs levels ≥10 IU/L, 97% ≥100 IU/L. The immunogenicity of hepatitis B vaccine after primary and booster vaccinations, administered in the four-dose scheme started at birth, was significantly higher (P< 0.05) than in the three-dose scheme started at birth. Hepatitis B vaccination according to the four-dose scheme started at month 3 produced significantly higher (P < 0.05) antibody levels in comparison to the four-dose scheme started directly after birth. This study showed that a fourdose hepatitis B vaccination scheme starting at month 3 resulted in the highest antibody levels of the three schemes investigated and can be recommended for incorporation in the Expanded Programme on Immunization in The Netherlands.     

Predictive value of neonatal MRI as compared to ultrasound in premature infants with mild periventricular white matter changes

A follow-up study was performed in 42 premature infants in whom serial neonatal ultrasound and a single neonatal MRI of the brain was normal, or showed mild periventricular white matter changes. The aim of the study was to evaluate the clinical significance of periventricular signal intensity changes on MRI and to compare the predictive value of neonatal MRI with that of ultrasound. The infants underwent repeated standardised motor assessments and developmental tests. MRI was repeated at the corrected age of 12 months. Pronounced periventricular signal intensity changes on neonatal MRI and periventricular echodensities (flaring) on ultrasound were associated with a high incidence of transient motor problems during infancy. The degree of echogenicity carried the highest predictive value, as compared to duration of flaring on ultrasound and degree of periventricular signal intensity change on MRI. It is concluded that signal intensity changes on neonatal MRI represent the same ischaemic change of the periventricular white matter as flaring on ultrasound and that routine neonatal MRI screening is not warranted in premature infants without clinical evidence of neurological problems and with normal or mildly abnormal ultrasound scans. Recording of the degree of echogenicity should become a routine procedure in neonatal cerebral ultrasonography.     

Malignant Cytological Washings from Radical Prostatectomy Specimens: A Possible Mechanism for Local Recurrence of Prostate Cancer Following Surgical Treatment of Organ Confined Disease

Purpose

Local recurrence of prostate cancer following complete and successful resection of organ confined disease has been variably reported in men. We hypothesized that observed secretions from the cut distal urethra during radical prostatectomy may contain malignant prostatic epithelial cells and contribute to this problem.

Materials and Methods

A prospective study was done of prostate cytology specimens from 50 consecutive men with clinically organ confined adenocarcinoma of the prostate undergoing radical retropubic or radical perineal prostatectomy. Direct cytological evaluation by 1 examiner was used to identify malignant or benign cells in these washings.

Results

Of 33 radical perineal and 17 radical retropubic prostatectomy specimens organ confinement was confirmed in 58 percent. Malignant prostatic epithelial cells were observed in 24 percent of all cytology specimens. Of cytological washings from prostates with pathologically confirmed organ confined cancers 17 percent showed malignant cells. While perineural invasion was noted in a majority of tumors with positive washings, only Gleason grade was a statistically significant predictor of recurrence (p = 0.009). Surgical approach did not alter the rate of positive cytology.

Conclusions

Malignant prostatic epithelial cells can be identified in the prostatic washings from men with pathologically organ confined prostate cancer. Surgical approach did not change the cytological findings. Gleason grade is a statistically significant predictor of cytological malignancy. These cells may represent a mechanism of failure following successful radical prostatectomy.